4-(1H-indol-1-yl)-1-piperidinyl derivatives

Abstract

PCT No. PCT/EP96/00363 Sec. 371 Date Jun. 27, 1997 Sec. 102(e) Date Jun. 27, 1997 PCT Filed Jan. 23, 1996 PCT Pub. No. WO96/23784 PCT Pub. Date Aug. 8, 1996The present invention concerns the compounds of formula the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein the dashed line designates an optional bond; R1 and R2 are each independently hydrogen, halogen, C1-6alkyl or C1-6alkyloxy; R3 and R4 are each independently hydrogen, C1-6alkyl, phenyl or phenyl substituted with one, two or three substituents selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, mercapto, amino, mono- and di(C1-6alkyl)-amino, carboxyl, C1-6alkyloxycarbonyl and C1-6alkylcarbonyl; Alk is C1-4alkanediyl; D is a pyrimidinone, piperidone or a benzimidozolidinone; having antipsychotic activity; their preparation, compositions containing them and their use as a medicine.

We claim: 
     
       1. A compound of formula ##STR13## a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, wherein: the dashed line designates an optional bond;   R 1  and R 2  are each independently hydrogen, halogen, C 1-6  alkyl or C 1-6  alkyloxy;   R 3  and R 4  are each independently hydrogen, C 1-6  alkyl, phenyl or phenyl substituted with one, two or three substituents selected from halo, hydroxy, nitro, cyano, trifluoromethyl, C 1-6  alkyl, C 1-6  alkyloxy, C 1-6  alkylthio, mercapto, amino, mono- and di(C 1-6  alkyl)amino, carboxyl, C 1-6  alkyloxycarbonyl and C 1-6  alkylcarbonyl;   Alk is C 1-4  alkanediyl;   D is a radical of formula ##STR14## wherein R 5  is hydrogen or C 1-6  alkyl; R 6  is hydrogen, C 1-6  alkyl, C 1-6  alkyloxy, C 1-6  alkylthio, amino or mono- or di(C 1-6  alkyl)amino; and   R 7  is hydrogen or C 1-6  alkyl; or   R 6  and R 7  taken together may form a bivalent radical --R 6  --R 7  --, in particular, --R 6  --R 7  -- may be ##STR15## wherein one or two hydrogen atoms of said radicals (a-1) to (a-5) each independently may be replaced by C 1-6  alkyl, hydroxy, C 1-6  alkyloxy or C 1-6  alkylcarbonyloxy; or --R 6  --R 7  -- may also be ##STR16## wherein one or where possible two or three hydrogen atoms in said radicals (a-6) to (a-14) each independently may be replaced by C 1-6  alkyl; or D is a radical of formula ##STR17## wherein R 8  is hydrogen or C 1-6  alkyl.         
     
     
       2. A compound according to claim 1, wherein D is a radical of formula ##STR18## wherein R 5  is defined as in claim 1; R 9  and R 10  each independently are hydrogen or C 1-6  alkyl; R 11  is C 1-6  alkyl, hydroxy, C 1-6  alkyloxy or C 1-10  alkylcarbonyloxy; and R 12  is hydrogen, C 1-6  alkyl, C 1-6  alkyloxy, C 1-6  alkylthio, amino or mono- or di(C 1-6  alkyl)amino. 
     
     
       3. A compound according to claim 1, wherein Alk is C 2-4  alkanediyl. 
     
     
       4. A compound according to claim 1, wherein R 1  is hydrogen or halogen and R 2  is hydrogen. 
     
     
       5. A compound according to claim 1, wherein the compound is selected from 3- 2- 4-(5-fluoro-1H-indol-1-yl)-1-piperidinyl!ethyl!-6,7,8,9-tetrahydro-2-methyl-4H-pyrido 1,2-a!pyrimidin-4-one;   6- 2- 4-(5-fluoro-1H-indol-1-yl)-1-piperidinyl!ethyl!-7-methyl-5H-thiazolo- 3,2-a!-pyrimidin-5-one;   5- 2- 4-(5-fluoro-1H-indol-1-yl)-1-piperidinyl!ethyl!-3,6-dimethyl-2-(methylamino)-4(3H)-pyrimidinone; and   2,3-dihydro-6- 2- 4-(1H-indol-1-yl)-1-piperidinyl!ethyl!-7-methyl-5H-thiazolo- 3,2-a!pyrimidin-5-one; a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof.   
     
     
       6. A composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 1. 
     
     
       7. A composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 2. 
     
     
       8. A composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 3. 
     
     
       9. A composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 4. 
     
     
       10. A composition comprising a pharmaceutically acceptable carrier and, as active ingredient, a therapeutically effective amount of a compound as claimed in claim 5. 
     
     
       11. A method of treating psychotic diseases in patients in need of the same which comprises administering to said patients a therapeutically effective amount of a compound as claimed in claim 1. 
     
     
       12. A method of treating psychotic diseases in patients in need of the same which comprises administering to said patients a therapeutically effective amount of a compound as claimed in claim 2. 
     
     
       13. A method of treating psychotic diseases in patients in need of the same which comprises administering to said patients a therapeutically effective amount of a compound as claimed in claim 3. 
     
     
       14. A method of treating psychotic diseases in patients in need of the same which comprises administering to said patients a therapeutically effective amount of a compound as claimed in claim 4. 
     
     
       15. A method of treating psychotic diseases in patients in need of the same which comprises administering to said patients a therapeutically effective amount of a compound as claimed in claim 5.